The stimulation of antigen-specific murine and human T cell hybridomas is generally accompanied by the elaboration of a variety of lymphokines. We have determined that the signal(s) transmitted via the antigen-specific receptor also affect the growth of these transformed cells. Within 24 hours of exposure to the appropriate antigen and antigen-presenting cells, T cell hybridomas develop an irreversible block between the G1 and S phases of the cell cycle and cease their spontaneous growth. In a mixed population of cells, the cell cycle block is manifested only in the antigen-stimulated cell, suggesting that it is not simply the result of the release of "toxic" lymphokines. This in vitro phenomenon can also be elicited by activating murine T cell tumors with a variety of agents, including Con A and certain anti-Thy 1 antibodies, that are known to induce normal T cells to produce interleukin 2 and proliferate. Furthermore, the in vivo growth of several antigen-specific T cell hybridomas has been studied in a mouse tumor model. Introduction of the tumor (subcutaneously) and of the appropriate antigen (intraperitoneally) results in complete rejection of the neoplasm. There appears to be two distinct mechanisms of rejection: (1) an acute inhibition of tumor growth due to activation of the cells and (2) a long-term immunity that develops in the treated mice. The significance of this project lies in two areas: (1) understanding the factors that control and/or contribute to the growth of neoplastic lymphocytes, and (2) a possible therapeutic role in the treatment of certain neoplastic diseases for agents that are normally considered to be stimulatory.